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1.
Crit Rev Biotechnol ; : 1-20, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830823

RESUMO

The rise of infectious diseases as a public health concern has necessitated the development of rapid and precise diagnostic methods. Imaging techniques like nuclear and optical imaging provide the ability to diagnose infectious diseases within the body, eliminating delays caused by sampling and pre-enrichments of clinical samples and offering spatial information that can aid in a more informed diagnosis. Traditional molecular probes are typically created to image infected tissue without accurately identifying the pathogen. In contrast, oligonucleotides can be tailored to target specific RNA sequences, allowing for the identification of pathogens, and even generating antibiotic susceptibility profiles by focusing on drug resistance genes. Despite the benefits that nucleic acid mimics (NAMs) have provided in terms of stabilizing oligonucleotides, the inadequate delivery of these relatively large molecules into the cytoplasm of bacteria remains a challenge for widespread use of this technology. This review summarizes the key advancements in the field of oligonucleotide probes for in vivo imaging, highlighting the most promising delivery systems described in the literature for developing optical imaging through in vivo hybridization.

2.
Vet Surg ; 53(1): 143-154, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37749853

RESUMO

OBJECTIVE: To investigate how tibial long axis (TLA) shift affects the postoperative tibial plateau angle (TPA) in four cranial closing wedge ostectomy (CCWO) techniques. STUDY DESIGN: In silico study. SAMPLE POPULATION: A total of 15 client-owned dogs. METHODS: Computed tomography (CT) scans of 15 client-owned dogs were reviewed using an open-source 3D computer graphics editor. Each computer-generated 3D tibia model underwent a CCWO, with cranial cortex alignment, in 10° increments up to 70° using each of the four previously described techniques. The TLA shift, TPA and mechanical tibial length (mTL) were calculated, using trigonometry, for each model. Equations for predicting final TPA were generated with linear regression. RESULTS: A total of 433 3D computer generated tibial models were analyzed. With each technique, the TPA varied in a linear fashion within the studied range of wedge angles. The TLA shift and tibial shortening magnitude varied between the four different CCWO techniques, with maximum mTL reduction of ranging from 7.5% to 40.9%. All predicted TPAs using the generated equations were within the target range of 4-6°. CONCLUSION: A linear relationship between ostectomy wedge angle and TPA correction was observed in this study, which allowed for generation of accurate corrective equations. CLINICAL SIGNIFICANCE: These results allow extrapolation of the wedge angle required to reach a postoperative TPA of 5°, by considering the TLA shift. The use of the generated corrective equations may thus increase CCWO planning precision.


Assuntos
Lesões do Ligamento Cruzado Anterior , Doenças do Cão , Humanos , Cães , Animais , Tíbia/cirurgia , Osteotomia/veterinária , Osteotomia/métodos , Tomografia Computadorizada por Raios X/veterinária , Período Pós-Operatório , Lesões do Ligamento Cruzado Anterior/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia
3.
Int Braz J Urol ; 50(4): 415-432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701185

RESUMO

INTRODUCTION: Chemotherapy and radiation therapy are considered standard treatments for stage II seminoma patients; however, these therapies are associated with long-term toxicities. Recently, retroperitoneal lymph node dissection has emerged as an alternative strategy, and the first three phase II trials were published in 2023 with promising results. The present study conducted a systematic review and meta-analysis to evaluate this surgery as an alternative treatment for stage IIA/B seminoma patients. PURPOSE: Seminomas are the most common testicular tumors, often affecting young adult males. Standard treatments for stage II seminomas include chemotherapy and radiation therapy, but these therapies are associated with long-term toxicities. Thus, identifying alternative strategies is paramount. Herein, we conducted a systematic review and meta-analysis to appraise the efficacy and safety of retroperitoneal lymph node dissection (RPLND) for treating this condition. METHODS: We systematically searched the PubMed, Embase, and Cochrane databases for studies evaluating RPLND as a primary treatment for stage II A/B seminomas. Using a random-effects model, single proportion and means and pooled 2-year recurrence-free survival rates with hazard rates and 95% CI were calculated. RESULTS: Seven studies were included, comprising 331 males with stage II seminomas. In the pooled analysis, the recurrence rate was 17.69% (95% CI 12.31-24.75), and the 2-year RFS rate was 81% (95% CI 0.77-0.86). The complication rate was 9.16% (95% CI 6.16-13.42), the Clavien-Dindo > 2 complication rate was 8.83% (95% CI 5.76-13.31), and the retrograde ejaculation rate was 7.01% (95% CI 3.54-13.40). The median operative time was 174.68 min (95% CI 122.17-249.76 min), median blood loss was 105.91 mL (95% CI 46.89-239.22 mL), and patients with no evidence of lymph node involvement ranged from 0-16%. CONCLUSIONS: Primary RPLNDs for treating stage IIA/B seminomas have favorable RFS rates, with low complication and recurrence rates. These findings provide evidence that this surgery is a viable alternative therapy for these patients.


Assuntos
Excisão de Linfonodo , Estadiamento de Neoplasias , Seminoma , Neoplasias Testiculares , Humanos , Excisão de Linfonodo/métodos , Seminoma/cirurgia , Seminoma/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Masculino , Espaço Retroperitoneal , Resultado do Tratamento , Intervalo Livre de Doença
4.
Sensors (Basel) ; 22(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36236204

RESUMO

Understanding how to seamlessly adapt the assistance of lower-limb wearable assistive devices (active orthosis (AOs) and exoskeletons) to human locomotion modes (LMs) is challenging. Several algorithms and sensors have been explored to recognize and predict the users' LMs. Nevertheless, it is not yet clear which are the most used and effective sensor and classifier configurations in AOs/exoskeletons and how these devices' control is adapted according to the decoded LMs. To explore these aspects, we performed a systematic review by electronic search in Scopus and Web of Science databases, including published studies from 1 January 2010 to 31 August 2022. Sixteen studies were included and scored with 84.7 ± 8.7% quality. Decoding focused on level-ground walking along with ascent/descent stairs tasks performed by healthy subjects. Time-domain raw data from inertial measurement unit sensors were the most used data. Different classifiers were employed considering the LMs to decode (accuracy above 90% for all tasks). Five studies have adapted the assistance of AOs/exoskeletons attending to the decoded LM, in which only one study predicted the new LM before its occurrence. Future research is encouraged to develop decoding tools considering data from people with lower-limb impairments walking at self-selected speeds while performing daily LMs with AOs/exoskeletons.


Assuntos
Exoesqueleto Energizado , Marcha , Humanos , Locomoção , Extremidade Inferior , Aparelhos Ortopédicos , Caminhada
5.
Phys Chem Chem Phys ; 23(5): 3311-3320, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33527930

RESUMO

We have obtained properties (or descriptors) of the transition states in the solvolysis of tert-butyl chloride, bromide and iodide. We show that all three transition states, in both protic and in aprotic solvents, are highly dipolar and are strong hydrogen bond acids and strong hydrogen bond bases, except for the tert-butyl iodide transition state in aprotic solvents, which has a rather low hydrogen bond acidity. Thus, the transition states are stabilized by solvents that are hydrogen bond bases (nucleophiles) and are hydrogen bond acids (electrophiles). We show also that the partition of the transition states between water and solvents is aided by both nucleophilic and electrophilic solvents and conclude that the rate of solvolysis of the three halides is increased by both nucleophilic and electrophilic solvents.

6.
Molecules ; 25(24)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353130

RESUMO

'Mencía'/'Jaen' it's an important red grape variety, exclusive of the Iberian Peninsula, used in wine production namely in Bierzo D.O. and Dão D.O., respectively. This work evaluates the effect of the two different "terroirs" on the phenolic composition and chromatic characteristics of 'Mencía'/'Jaen' monovarietal wines produced at an industrial scale in the same vintage. Using Principal Component Analysis (PCA), Partial Least Squares-Discrimination Analysis (PLS-DA), and Orthogonal PLS-DA (OPLS-DA) it was found that peonidin-3-coumaroylglucoside, petunidin-3-glucoside, malvidin-3-coumaroylglucoside, peonidin-3-glucoside, malvidin-3-acetylglucoside, malvidin-3-glucoside, and ferulic acid were the phenolic compounds with the highest differences between the two regions. PLS regression allowed to correlate the differences in lightness (L*) and redness (a*) of wines from 'Jaen' and 'Mencía' to differences in colored anthocyanins, polymeric pigments, total pigments, total anthocyanins, cyanidin-3-acetylglucoside, delphinidin-3-acetylglucoside, delphinidin-3-glucoside, peonidin-3-coumaroylglucoside, petunidin-3-glucoside and malvidin-3-glucoside in wines, and the colorless ferulic, caffeic, and coutaric acids, and ethyl caffeate. The wines a* values were more affected by colored anthocyanins, ferulic acid, total anthocyanins, delphinidin-3-acetylglucoside, delphinidin-3-glucoside and petunidin-3-acetylglucoside, and catechin. The positive influence of ferulic acid in the a* values and ferulic, caffeic, coutaric acids, and ethyl caffeate on the L* values can be due to the co-pigmentation phenomena. The higher dryness and lower temperatures during the September nights in this vintage might explain the differences observed in the anthocyanin content and chromatic characteristics of the wines.


Assuntos
Fenóis/análise , Vinho/análise , Análise Discriminante , Portugal , Análise de Componente Principal
7.
J Cancer Educ ; 34(3): 556-561, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29508229

RESUMO

Cancer literacy is currently one of the most important dimensions of cancer continuum. Objective assessment of cancer knowledge in populations remains a challenging field to public health entities. Different evaluation tools are currently available; still, some groups remain disregarded due to the absence of validated instruments. Cancer literacy in adolescents and young adults has been clearly overlooked being a subject that requires new tools to be properly studied. To address this topic, we developed a new instrument and field tested it in a classroom environment for internal reliability, construct, and face validity. "Students Knowledge and Perceptions about Cancer questionnaire" was designed in Portuguese language and adapted to the Portuguese context by a multidisciplinary team. The final version of the questionnaire includes 35 items organized in three sections, encompassing knowledge and perceptions about cancer and socio-biographic data. Cancer experts ensured content validity, while tailoring of contents was refined with high school teachers. Test and retest of the instrument showed a good reliability of the scale and construct validity. Also, the clarity of the questionnaire and suitability to proper evaluate cancer knowledge was consistent between test and retest. The Students' Knowledge and Perceptions About Cancer Questionnaire (SKPaC) showed to be a valid tool to assess adolescents' knowledge and perceptions about cancer that can be used in the educational context.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/etiologia , Neoplasias/prevenção & controle , Estudantes , Inquéritos e Questionários , Adolescente , Feminino , Letramento em Saúde , Humanos , Masculino , Portugal , Reprodutibilidade dos Testes
8.
J Cancer Educ ; 34(5): 847-853, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29931456

RESUMO

Cancer prevention should start as early as possible. Young adults would benefit largely from the use of a smartphone app aiming at promoting cancer prevention behaviours. The aims of the study described in this paper are to (1) examine the user participation and engagement with a cancer prevention app in real-life settings and (2) assess changes in the users' cancer prevention behaviours. A cancer prevention smartphone app called Happy was developed and released to the general population. Data from registered app users' (N = 3326) demographics and baseline cancer prevention behaviours was analysed. App engagement was measured and all behaviour data logged through the app was analysed to assess the effectiveness of the app in the promotion of cancer prevention behaviours. User demographics and baseline behaviour assessment show that the app reached its intended target population: young adults that generally do not comply with cancer prevention guidelines. Logged behavioural data showed an increased frequency in several cancer prevention behaviours and a significant increase in the overall putative cancer prevention level (p < 0.001). However, user engagement with the app was limited and might condition the long-term impact of such changes. Happy reached its intended population and seems to be an effective tool to promote cancer prevention. Further research is needed to fully assess its long-term persuasive potential.


Assuntos
Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Aplicativos Móveis/estatística & dados numéricos , Neoplasias/prevenção & controle , Neoplasias/psicologia , Comportamento de Redução do Risco , Smartphone/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
9.
J Org Chem ; 82(7): 3347-3358, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28207255

RESUMO

Since their discovery, crown ethers as well as the most recent carbon nanostructures, namely fullerenes, carbon nanotubes, and graphene, have received a lot of attention from the chemical community. Merging these singular chemical structures by noncovalent forces has provided a large number of unprecedented supramolecular assemblies with new geometric and electronic properties whose more representative examples are presented in this Synopsis organized according to the different nature of the carbon nanostructures.

10.
An Acad Bras Cienc ; 89(4): 2921-2929, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29236864

RESUMO

Biochemical markers produced by the affected organ or body in response to disease have gained high clinical value due to assess disease development and being excellent predictors of morbidity and mortality. The aim of this study is to analyze different biochemical markers in critically cancer patients and to determine which of them can be used as predictors of mortality. This is a prospective, cross-sectional study conducted at a University Hospital in Porto Alegre - RS. Screening was done to include patients in the study. Serum biochemical markers obtained in the first 24 hours of Intensive Care Unit hospitalization were analyzed. A second review of medical records occurred after three months objected to identify death or Unit discharged. A sample of 130 individuals was obtained (control group n = 65, study group n = 65). In the multivariate model, serum magnesium values ​​OR = 3.97 (1.17; 13.5), presence of neoplasia OR = 2.68 (95% CI 1.13; 6.37) and absence of sepsis OR = 0.31 (95% CI 0.12; 0.79) were robust predictors of mortality. The association of solid tumors, sepsis presence and alteration in serum magnesium levels resulted in an increased chance of mortality in critically ill patients.


Assuntos
Biomarcadores Tumorais/sangue , Estado Terminal/mortalidade , Neoplasias/mortalidade , Estudos Transversais , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos
11.
J Am Chem Soc ; 138(47): 15359-15367, 2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27640915

RESUMO

Two new conjugated porphyrin-based systems (dimers 3 and 4) endowed with suitable crown ethers have been synthesized as receptors for a fullerene-ammonium salt derivative (1). Association constants in solution have been determined by UV-vis titration experiments in CH2Cl2 at room temperature. The designed hosts are able to associate up to two fullerene-based guest molecules and present association constants as high as ∼5 × 108 M-1. Calculation of the allosteric cooperative factor α for supramolecular complexes [3·12] and [4·12] showed a negative cooperative effect in both cases. The interactions accounting for the formation of the associates are based, first, on the complementary ammonium-crown ether interaction and, second, on the π-π interactions between the porphyrin rings and the C60 moieties. Theoretical calculations have evidenced a significant decrease of the electron density in the porphyrin dimers 3 and 4 upon complexation of the first C60 molecule, in good agreement with the negative cooperativity found in these systems. This negative effect is partially compensated by the stabilizing C60-C60 interactions that take place in the more stable syn-disposition of [4·12].

12.
Angew Chem Int Ed Engl ; 54(4): 1255-60, 2015 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-25431361

RESUMO

A fullerene ammonium derivative has been combined with different metalloporphyrin-crown ether receptors to generate very stable supramolecules. The combination of fullerene-porphyrin and ammonium-crown ether interactions leads to a strong chelate effect as evidenced by a high effective molarity (3.16 M). The different parameters influencing the stability of the supramolecular ensembles, in particular the nature of the metal in the porphyrin moiety, have been rationalized with the help of theoretical calculations thus providing new insights into fullerene-porphyrin interactions.

13.
Hepatogastroenterology ; 61(129): 18-21, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24895786

RESUMO

BACKGROUND/AIMS: Benefits of using laparoscopic cholecystectomy (LC) in the elderly with acute cholecystitis (AC) is still questionable. Our aim is to carry out a comparative analysis of that intervention in two groups of patients: under 65 years old, and over or equal to 65 years old. METHODOLOGY: This study corresponds to 249 LCs carried out during 4 years at the Emergency and Surgery Department of Hospital de S. João; 2 groups of individuals were considered: group A--under 65 years old, and group B--65 years old or over. The first consisted of 168 cases (88 men and 80 women, mean age 48.34 years (+/- 11.80)); and the second included 81 patients (40 men and 41 women, mean age 75.73 years (+/- 6.87)). The diagnosis was made on the basis of clinical symptoms, leukocytosis and ultrasound. RESULTS: The comparative analysis between these two groups provided the following results: 1) Mortality: 0% in A vs. 4.76% in B (P = 0.007); 2) Overall postoperative complications: 5.36% in A vs. 22.2% in B (P < 0.001); 3) Surgical complications: 4.76% in A vs. 14.8% in B (P = 0.468); 4) Intraoperative complications: 4.76% in A vs. 4.94% in B (P = 0.007); 5) Reoperations: 2.98% in A vs. 7.41% in B (P = 0.022); 6) Conversion: 12.50% in A vs. 17.28% in B (P = 0.447); 7) Lesion of the Main Bile Duct: 1.79% in A vs. 2.47% in B (P = 0.447); 8) Hospital Stay, equal to or less than 4 days: 72.62% in A vs. 27.16% in B (P <0.001). CONCLUSIONS: LC is a safe and efficient intervention in the treatment of acute cholecystitis in the elderly, although with greater morbidity and longer hospital stay, when compared with younger patients.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Resultado do Tratamento
14.
Food Res Int ; 190: 114558, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945562

RESUMO

Fermented beverages, including wine, can accumulate high concentrations of biogenic amines (BAs), which can pose potential health risks. BAs are produced by various yeasts and lactic acid bacteria (LAB) during winemaking. LAB are the main contributors to the formation of histamine and tyramine, the most toxic and food safety relevant biogenic amines. Numerous factors, ranging from agricultural and oenological practices to sanitation conditions, can contribute to the formation of BAs in wines. Moreover, organic and biodynamic wines impose limitations on the use of common food additives employed to control the proliferation of native and spoilage microorganisms during vinification and storage. To mitigate histamine production, commercial starter cultures incapable of synthesising histamine have been effectively utilised to reduce wine histamine content. Alternative fermentative microorganisms are currently under investigation to enhance the safety, quality, and typicity of wines, including indigenous LAB, non-Saccharomyces yeasts, and BAs degrading strains. Furthermore, exploration of extracts from BAs-degrading microorganisms and their purified enzymes has been undertaken to reduce BAs levels in wines. This review highlights microbial contributors to BAs in wines, factors affecting their growth and BA production, and alternative microorganisms that can degrade or avoid BAs. The aim is to lessen reliance on additives, providing consumers with safer wine choices.


Assuntos
Aminas Biogênicas , Fermentação , Vinho , Leveduras , Vinho/análise , Vinho/microbiologia , Aminas Biogênicas/análise , Leveduras/metabolismo , Microbiologia de Alimentos , Histamina/análise , Histamina/metabolismo , Tiramina/análise , Lactobacillales/metabolismo
15.
Mol Ther Nucleic Acids ; 35(1): 102122, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38333674

RESUMO

Antimicrobial resistance (AMR) is a growing concern because it causes microorganisms to develop resistance to drugs commonly used to treat infections. This results in increased difficulty in treating infections, leading to higher mortality rates and significant economic effects. Investing in new antimicrobial agents is, therefore, necessary to prevent and control AMR. Antimicrobial nucleic acids have arisen as potential key players in novel therapies for AMR infections. They have been designed to serve as antimicrobials and to act as adjuvants to conventional antibiotics or to inhibit virulent mechanisms. This new category of antimicrobial drugs consists of antisense oligonucleotides and oligomers, DNAzymes, and transcription factor decoys, differing in terms of structure, target molecules, and mechanisms of action. They are synthesized using nucleic acid analogs to enhance their resistance to nucleases. Because bacterial envelopes are generally impermeable to oligonucleotides, delivery into the cytoplasm typically requires the assistance of nanocarriers, which can affect their therapeutic potency. Given that numerous factors contribute to the success of these antimicrobial drugs, this review aims to provide a summary of the key advancements in the use of oligonucleotides for treating bacterial infections. Their mechanisms of action and the impact of factors such as nucleic acid design, target sequence, and nanocarriers on the antimicrobial potency are discussed.

16.
Am J Hosp Palliat Care ; : 10499091241234859, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378258

RESUMO

Background: 37.5% of deaths in our area occur in hospital. There are known high unmet needs of adult patients dying in hospital, this unmet need can be reduced by using an individualised care plan and specialist palliative care review. Intervention: In 2022 UHSussex developed an electronic comfort observation chart and individualised care plan, with a centralised dashboard allowing Palliative Care Teams (SPCT) to view trends, target interventions, and a rolling prospective audit. Results: 3000 patients have had their care supported with electronic comfort observations (e-comfort obs). Over 72% of all deaths in the Trust in the last 3 months have been on e-comfort obs, with 2/3 of all deaths in the first 12 months on e-comfort obs. The average length of time on e-comfort obs is 4 days resulting in 70,000 sets of e-comfort obs recorded since launch. Seven percent of e-comfort obs record moderate or severe symptoms. We have identified benefits to people who are dying, those important to them, ward staff, SPCT and on a systems level. Conclusion: E-comfort obs can be successfully embedded in a large acute Trust. This development should improve quality of end of life care in our hospitals both for individuals and for future patients, through on-going targeted education and intervention. Further work is needed to develop the system further including integrating data from electronic prescribing.

17.
J Glob Infect Dis ; 16(1): 13-18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680757

RESUMO

Introduction: Understanding the epidemiology and cost implications of acute bacterial meningitis is crucial for effective health planning, timely treatment implementation, and comprehensive patient support measures, as well as for determining appropriate hospital expenses. Therefore, we conducted an analysis of hospitalization cases for bacterial meningitis in Brazil from January 2008 to December 2019. Methods: This is a descriptive ecological study that utilized the Hospital Information System of Brazil's National Unified Health System (SIH/SUS) database. The variables included sex, region, age group, hospitalizations, deaths, lethality rate, and hospital service expenses. The data were tabulated to focus specifically on the epidemiological aspect of bacterial meningitis. Results: During the study period, there were 20,207 hospitalizations for bacterial meningitis in Brazil. Men accounted for a higher number of cases, with 11,690 (57.67%), while women had a higher lethality rate of 10.64%. The Southeast region had the highest percentage of both hospitalizations (45.78%) and deaths (46.42%). Bacterial meningitis remains an important cause of morbidity and mortality, particularly in children under 5 years of age. Notably, the elderly and the Northeast region showed higher rates of lethality. The total expenditure on hospital services exceeded 43 million in Brazilian real, with the highest expenditure observed in 2019 and the lowest in 2011. Conclusion: A higher prevalence of the disease was observed in males, in children under 1-year-old and in the southeast region. Hospital expenditures were found to be substantial and increasing over time, underscoring the significance of early diagnosis and the promotion of vaccination campaigns.

18.
Neuron ; 112(14): 2333-2348.e6, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38692278

RESUMO

Molecular layer interneurons (MLIs) account for approximately 80% of the inhibitory interneurons in the cerebellar cortex and are vital to cerebellar processing. MLIs are thought to primarily inhibit Purkinje cells (PCs) and suppress the plasticity of synapses onto PCs. MLIs also inhibit, and are electrically coupled to, other MLIs, but the functional significance of these connections is not known. Here, we find that two recently recognized MLI subtypes, MLI1 and MLI2, have a highly specialized connectivity that allows them to serve distinct functional roles. MLI1s primarily inhibit PCs, are electrically coupled to each other, fire synchronously with other MLI1s on the millisecond timescale in vivo, and synchronously pause PC firing. MLI2s are not electrically coupled, primarily inhibit MLI1s and disinhibit PCs, and are well suited to gating cerebellar-dependent behavior and learning. The synchronous firing of electrically coupled MLI1s and disinhibition provided by MLI2s require a major re-evaluation of cerebellar processing.


Assuntos
Interneurônios , Inibição Neural , Células de Purkinje , Animais , Células de Purkinje/fisiologia , Interneurônios/fisiologia , Inibição Neural/fisiologia , Camundongos , Cerebelo/citologia , Cerebelo/fisiologia , Camundongos Transgênicos , Potenciais de Ação/fisiologia , Camundongos Endogâmicos C57BL , Córtex Cerebelar/fisiologia , Córtex Cerebelar/citologia
19.
Front Cardiovasc Med ; 10: 1272897, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075956

RESUMO

Aims: Investigate whether a Home-based Exercise Therapy (HBET) program for patients with Peripheral Arterial Disease (PAD) and Intermittent Claudication (IC) with a behavior change intervention, supported by a smartphone application, is effective in improving walking distances and performance, and quality of life (QoL) over 6 months. Methods and results: This was a single-center, prospective, two-arm, single-blinded randomized controlled trial including 73 patients with PAD and IC, and three assessment moments: baseline, 3, and 6 months. Participants were randomized to receive a walking exercise prescription, with the support (n = 38) or without the support (n = 35) of the WalkingPad app, between January 2021 and July 2022. Both groups received two face-to-face behavior change sessions and 12 structured and targeted reinforcement phone calls over 6 months. Primary outcomes were between-group differences in pain-free walking distance (PFWD), functional walking distance (FWD), maximal walking distance (MWD), and 6-min walk distance (6 MWD) at 3 and 6 months. Secondary outcomes were QoL and walking impairment. Seventy-three patients (mean age 64 ± 7.2 years, 88% men) participated in this study, 60 of whom completed the three assessment moments. The whole sample significantly improved all primary outcomes in the first 3 months; that is, the average PFWD (151.1 m), FWD (175.2 m), MWD (171.1 m), and 6 MWD (30.8 m) increased from T1 to T2. Only MWD exhibited a significant average increase (35.0 m). Secondary outcomes also increased from baseline to 3 and 6 months. There were no between-group differences, except for MWD, which showed a greater increase at 6 months in the group that used the app, excluding patients with weak walking ability and extreme anxiety symptoms at baseline. Conclusion: The intervention improved distances and walking skills as well as the physical, mental, and disease-related quality of life among adults with PAD and IC. The group that used the WalkingPad app improved their MWD in 6 months compared to the control group, except for patients with poor walking ability and extreme anxiety symptoms, which suggests the effectiveness of the WalkingPad app for patients with high walking ability and no severe anxiety symptoms. More research is needed to determine the durability of these findings and to explore what app functionality might promote the other outcomes. Clinical Trial Registration: https://clinicaltrials.gov (NCT04749732).

20.
Biomater Sci ; 11(2): 499-508, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36458466

RESUMO

Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(D,L-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 µg mL-1, corresponding to 16.3 µg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 µg mL-1 against Pseudomonas aeruginosa, and 16-32 µg mL-1 against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for P. aeruginosa and from 6-8 h to 0.5-1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.


Assuntos
Peptídeos Antimicrobianos , Nanopartículas , Staphylococcus aureus , Polímeros/química , Polietilenoglicóis/química , Nanopartículas/química , Tamanho da Partícula , Portadores de Fármacos/química
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